Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results—namely high-risk human papillomavirus (HPV) ...infection and cytohistopathology—predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer.
We did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL.
Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16·5, 95% CI 14·2–19·2, p<0·0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4·4, 3·7–5·3, p<0·0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% 101/228 for cervical cancer in HIV-negative women (PR vs normal cytology 14·1, 11·1–17·9, p<0·0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% 11/527 in cervical high-risk HPV-negative women up to 24% 33/138 in cervical HPV16-positive women; PR 12·9, 95% CI 6·7–24·8, p<0·0001) and HIV-positive women (from 8% 84/1094 to 17% 31/186; 2·3, 1·6–3·4, p<0·0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% 5/498 in normal cytology up to 22% 59/273 in cervical HSIL; PR 23·1, 9·4–57·0, p<0·0001) and HIV-positive women (from 7% 105/1421 to 25% 25/101; 3·6, 2·5–5·3, p<0·0001). Prevalence of HPV16-positive anal HSIL was 23–25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women).
HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women.
International Agency for Research on Cancer.
Among virally suppressed HIV-infected persons, we examined the relationship between obesity and alterations in key clinical markers of immune activation and inflammation. These markers have also been ...associated with excess HIV-related cardiovascular disease and mortality.
We evaluated data from virally suppressed participants in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy, including inflammatory biomarkers (interleukin-6 and highly sensitive C-reactive protein), monocyte biomarkers soluble CD163 (sCD163), sCD14, and monocyte immunophenotypes. We assessed associations with these immunologic measures and obesity, via logistic regression preadjustment and postadjustment for demographic and clinical factors, homeostatic model assessment of insulin resistance, and leptin levels.
Among 452 evaluable participants, median (interquartile range) age was 41 (36-48) years, CD4 cell count was 475 (308-697) cells/μl, and 21% were obese (BMI ≥ 30 kg/m). In univariable models, obesity, smoking, and lower CD4 cell count were associated with higher measures of inflammation and monocyte activation. After adjustment, obesity remained independently associated with elevated levels (highest vs. lower two tertiles) of interleukin-6 odds ratio (OR) 1.96; P = 0.02, highly sensitive C-reactive protein (OR 2.79; P < 0.001) and sCD163 (OR 1.94; P = 0.02), and elevated frequency of CD14CD16 (OR 1.77; P = 0.03) and CD14dimCD16 (OR 1.97; P = 0.01). Adjusting for homeostatic model assessment of insulin resistance and leptin modestly affected associations for obesity with inflammation and monocyte activation.
Obesity was prevalent and independently associated with greater monocyte activation and systemic inflammation. Research is needed to determine how adipose tissue excess is functionally related to persistent immunologic abnormalities among HIV-infected persons with viral suppression.
Background. Persons with human immunodeficiency virus (HIV) infection are at risk for premature cardiovascular disease (CVD). Predictors of atherosclerotic disease progression in contemporary ...patients have not been well described. Methods. Using data from a prospective observational cohort of adults infected with HIV (Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy), we assessed common carotid artery intima-media thickness (CIMT) at baseline and year 2 by ultrasound. We examined HIV-associated predictors of CIMT progression after adjusting for age, sex, race/ethnicity, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol level, and baseline CIMT using linear regression. Results. Among 389 participants (median age at baseline, 42 years; male sex, 77%; median CD4+ cell count at baseline, 485 cells/mm 3 ; 78% receiving antiretroviral therapy), the median 2-year CIMT change was 0.016 mm (interquartile range, -0.003 to 0.033 mm; P <.001). Lesser CIMT progression was associated with a suppressed viral load at baseline (-0.009 mm change; P =.015) and remaining virologically suppressed throughout follow-up (-0.011 mm changes; P <.001). After adjusting for additional risk factors and a suppressed viral load during follow-up, nonnucleoside reverse transcriptase inhibitor versus protease inhibitor exposure was associated with lesser CIMT progression (-0.011 mm change; P =.02). Conclusions. Suppressing HIV replication below clinical thresholds was associated with less progression of atherosclerosis. The proatherogenic mechanisms of HIV replication and the net CVD benefit of different antiretroviral drugs should be a focus of future research.
Background. Adherence of 95% or greater to highly active combination antiretroviral therapy is generally considered necessary to achieve optimal virologic suppression in HIV-infected patients. ...Understanding factors associated with poor adherence is essential to improve patient compliance, maximize virologic suppression, and reduce morbidity and mortality.
Methods. We evaluated baseline data from 528 patients taking antiretrovirals, enrolled from March 2004 to June 2006, in a multicenter, longitudinal, prospective cohort study (the SUN study). Using multiple logistic regression, we examined independent risk factors for non-adherence, defined as reporting having missed one or more antiretroviral doses in the past three days on the baseline questionnaire.
Results. Of 528 participants (22% female, 28% black, median age 41 years, and median CD4 cell count 486 cells/mm
3
), 85 (16%) were non-adherent. In the final parsimonious multivariate model, factors independently associated with non-adherence included black race (adjusted odds ratio (aOR): 2.08, 95% confidence interval (CI): 1.20-3.60 vs. white race), being unemployed and looking for work (aOR: 2.03, 95% CI: 1.14-3.61 vs. all other employment categories), having been diagnosed with HIV ≥5 years ago (aOR: 1.95, 95% CI: 1.18-3.24 vs. being HIV-diagnosed <5 years ago), drinking three or more drinks per day (aOR: 1.73, 95% CI: 1.02-2.91 vs. drinking <3 drinks per day), and having not engaged in any aerobic exercise in the last 30 days (aOR: 2.13, 95% CI: 1.25-3.57).
Conclusion. Although the above factors may not be causally related to non-adherence, they might serve as proxies for identifying HIV-infected patients at greatest risk for non-adherence who may benefit from additional adherence support.
Background. Anal cancer rates are higher for human immunodeficiency virus (HIV)–infected adults than for uninfected adults. Limited published data exist characterizing the incidence of precursor ...lesions detected by anal cytology. Methods. The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in 4 US cities. At baseline and annually thereafter, each participant completed a behavioral questionnaire, and healthcare professionals collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping. Results. Among 243 participants with negative baseline results of anal cytology, 37% developed abnormal cytology findings (incidence rate, 13.9 cases/100 person-years of follow-up; 95% confidence interval CI, 11.3–16.9) over a median follow-up duration of 2.1 years. Rates among men having sex with men, among women, and among men having sex with women were 17.9 cases/person-years of follow-up (95% CI, 13.9–22.7), 9.4 cases/person-years of follow-up (95% CI, 5.6–14.9), and 8.9 cases/person-years of follow-up (95% CI, 4.8–15.6), respectively. In multivariable analysis, the number of persistent high-risk HPV types (adjusted hazard ratio aHR, 1.17; 95% CI, 1.01–1.36), persistent high-risk HPV types except 16 or 18 (aHR, 2.46; 95% CI, 1.31–4.60), and persistent types 16 or 18 (aHR, 3.90; 95% CI, 1.78–8.54) remained associated with incident abnormalities. Conclusions. The incidence of abnormal anal cytology findings was high and more likely to develop among persons with persistent high-risk HPV.
Treatment of human immunodeficiency virus (HIV) infection with highly active combination antiretroviral therapy has increased survival and shifted the spectrum of HIV-associated morbidity and ...mortality from opportunistic infections toward a variety of other medical conditions. The prospective cohort Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study) monitors the clinical course of HIV-infected individuals treated with combination antiretroviral therapy in 4 US cities. Every 6 months, clinical assessments, medical record abstraction, audio computer-assisted self-interview, and neurocognitive measurements are completed and blood and urine specimens are banked centrally. At enrollment and periodically thereafter, additional techniques such as anal cytology, dual energy x-ray absorptiometry, carotid ultrasonography, echocardiography, and abdominal and cardiac computed tomography are performed. From March 2004 through June 2006, 700 participants were enrolled; median age was 41 years, 76% were men, 58% were non-Hispanic white, 62% were men who have sex with men, 78% were taking combination antiretroviral therapy (of whom 86% had an HIV viral load of <400 copies/mL), and median CD4+ T-lymphocyte count was 459 cells/mm3 (interquartile range: 324–660). The SUN Study provides a wealth of data that will inform and improve the clinical management of HIV-infected individuals in the modern era.
Information about vulvovaginal and perianal condylomata acuminata and intraepithelial neoplasia in women infected with HIV-1 is needed to develop guidelines for clinical care. Our aim was to ...investigate the incidence of these lesions in HIV-1-positive and HIV-1-negative women and to examine risk factors for disease.
In a prospective cohort study, 925 women had a gynaecological examination twice yearly—including colposcopy and tests for human papillomavirus DNA in cervicovaginal lavage—for a median follow-up of 3·2 years (IQR 0·98–4·87).
Vulvovaginal and perianal condylomata acuminata or intraepithelial neoplasia were present in 30 (6%) of 481 HIV-1-positive and four (1%) of 437 HIV-1-negative women (p<0·0001) at enrolment. Women without lesions at enrolment were included in an incidence analysis. 33 (9%) of 385 HIV-1-positive and two (1%) of 341 HIV-1-negative women developed vulvovaginal or perianal lesions, resulting in an incidence of 2·6 and 0·16 cases per 100 person-years, respectively (relative risk 16, 95% CI 12·9–20·5; p<0·0001). Risk factors for incident lesions included HIV-1 infection (p=0·013), human papillomavirus infection (p=0·0013), lower CD4 T lymphocyte count (p=0·0395), and history of frequent injection of drugs (p=0·0199).
Our results suggest that HIV-1-positive women are at increased risk of development of invasive vulvar carcinoma. Thus, we recommend that, as part of every gynaecological examination, HIV-1-positive women should have a thorough inspection of the vulva and perianal region, and women with abnormalities—except for typical, exophytic condylomata acuminata—should undergo colposcopy and biopsy.
In the combination antiretroviral therapy (cART) era, renal dysfunction remains common. The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) ...(ClinicalTrials.gov number, NCT00146419) is a prospective observational cohort study of HIV-infected adults. At baseline, comprehensive data were collected, including cystatin C and measures of renal function. Univariate and multivariate regression analyses were performed to identify factors associated with baseline renal dysfunction estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m(2) calculated using the simplified Modification of Diet in Renal Disease equation and elevated cystatin C (>1.0 mg/liter) in a cross-sectional analysis. Among 670 subjects with complete data (mean age 41 years, mean CD4 cell count 530 cells/mm(3), 79% prescribed cART), the mean eGFR was 96.8 ml/min/1.73 m(2). Forty percent of subjects had renal dysfunction; 3.3% had chronic kidney disease (eGFR < 60 ml/min/1.73 m(2)). Elevated cystatin C was present in 18% of subjects. In multivariate analysis, renal dysfunction was associated with older age, non-Hispanic white race/ethnicity, higher body mass index (BMI), hypertension, higher cystatin C levels, and current prescription of ritonavir. Factors associated with elevated cystatin C included hepatitis C coinfection, hypertension, current smoking, older age, current tenofovir use, detectable plasma HIV RNA, and elevated microalbuminuria. The prevalence of chronic kidney disease (CKD) was low in this contemporary HIV cohort. However, mild to moderate renal dysfunction was common despite the widespread use of cART.
In this study, the correlations of human immunodeficiency virus type 1 (HIV-1) RNA levels in blood plasma, vaginal secretions, and cervical mucus of 52 HIV-1-infected women were determined. The ...amount of cell-free HIV-1 RNA in blood plasma was correlated with that in vaginal secretions (Spearman's rank correlation coefficient (r) = 0.64 P < .001 In both blood plasma and vaginal secretions, the amounts of cell-free and cell-associated HIV-1 RNA were highly correlated (r = 0.76, P < .01 and r = 0.85, P < .01, respectively). Cell-free HIV-1 RNA levels in blood plasma and vaginal secretions were negatively correlated with CD4+ T lymphocyte count (r = −0.44, P < .01 and r = −0.40, P < .01, respectively). Similar to the effect observed in blood plasma, initiation of antiretroviral therapy significantly reduced the amount of HIV-1 RNA in vaginal secretions. These findings suggest that factors that lower blood plasma virus load may also reduce the risk of perinatal and female-to-male heterosexual transmission by lowering vaginal virus load.
Most human immunodeficiency virus type 1 (HIV-1) transmission worldwide is the result of exposure to infectious virus in genital secretions. However, current vaccine candidates are based on virus ...isolates from blood. In this study, vaginal secretions from HIV-1–infected women were examined for evidence of cellular viral replication that produced virus with properties different from that in blood. Multiply spliced HIV-1 messenger RNA, which is found only in cells replicating virus, was detected in all vaginal lavage samples tested. There was a strong correlation between the amounts of multiply spliced HIV-1 messenger RNA and of cell-free HIV-1 RNA in the lavage samples. In addition, significant genotypic differences were found in cell-free virus from matched blood plasma and vaginal secretions. Moreover, drug resistance–associated mutations appeared in plasma virus several months before appearing in vaginal virus. These findings indicate that cellular replication of HIV-1 occurs in vaginal secretions and can result in a virus population with important differences from that in blood
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